Tissue distribution and polymorphism of minor histocompatibility antigens involved in GVHR

Abstract

A graft-vs-host reaction (GVHR) develops after major histocompatibility complex (MHC)-compatible bone marrow-transplantation. In the genetic combination studied, B10.D2 donor cells differed from those of (DBA/2 x B10.D2)F1 mice for multiple DBA/2 minor histocompatibility antigens (mHAg) and minor lymphocyte stimulating (Mls) antigens. We investigated the distribution and the cell type expression of mHAg in tissues that were potential GVHR targets, by means of specific T-cell clones derived from mice undergoing reaction. The T-cell clones studied had a CD4+ phenotype and recognized 12 distinct mHAg that were not be product of the Mls-1a gene and that were presented predominantly in association with MHC class II A molecules. Our results indicate that DBA/2 alleles coding for mHAg are frequent in both laboratory and geographically unrelated wild mice. Each mHAg displays an individual pattern of expression on cells present in thymus, skin, gut, and liver. In addition, chimeric mice and established cell lines allowed the identification of cell types expressing mHAg. We found that most mHAg are present on lymphoid and monocyte-macrophage cells, whereas one, distinguished by its absence from lymphoid cells and damaged tissues, is expressed by monocyte-macrophage cells.